This is a Midcareer Investigator Award in Patient-Oriented Research (POR) application (K24) for Stuart R. Lessin, M.D and will focus on cutaneous oncology. Dr. Lessin is Associate Professor and Co-Director of the Cutaneous Lymphoma Program in the Department of Dermatology at the University of Pennsylvania. He is highly committed to POR and has a well established track record (funding and publications) in the area of cutaneous T-cell lymphoma (CTCL). He has developed techniques for the molecular diagnosis of lymphoproliferative skin diseases based on T-cell receptor (TCR) gene expression and translated them into new strategies of therapy utilizing the TCR as a target. Dr. Lessin is currently the principal investigator of a FDA funded Phase I clinical trial testing the safety and efficacy of genetic (DNA) vaccination of human TCR in patients with CTCL. The overall research goal of this proposal will be to develop and test novel therapeutic approaches to skin cancers utilizing the technologies of therapeutic DNA vaccines, peptide vaccines and peptidomimetics. Dr. Lessin has been heavily involved in the mentoring and training of trainees in POR at all levels - medical students, residents/fellows and junior faculty. This has been accomplished through a series of well established POR programs. Currently, Dr. Lessin serves as a mentor in the Department of Dermatology's Cutaneous Oncology Fellowship Program, NIH Training Grant (T32), Drug Study Unit, Derm 800 Research elective and Junior Faculty Mentor's Program. The University of Pennsylvania's commitment and ability to provide opportunities and facilities necessary for POR is extraordinary. A well established Core Curriculum in POR Training, a NIH sponsored General Clinical Research Center (GCRC) and outstanding interaction between basic and clinical investigators provides a unique and dynamic environment in which to conduct and train individuals in POR. Dr. Lessin will participate in the POR core curriculum and the GCRC. This award will provide a critical infrastructure for Dr. Lessin to pursue POR and to mentor other investigators in POR. A commitment of 50 percent effort will ensure the continued acquisition of funding and protected time for clinical testing of new therapies. Furthermore, it will enable Dr. Lessin to continue to participate in the ongoing departmental and institutional POR programs and serve as a role model and mentor for young investigators in POR at the University of Pennsylvania.